The long-term objective of the proposed research is to develop a novel, non-invasive tool for microscopic imaging of superficial lesions, including cancers and burns. The short-term goal is to apply the proposed technology in small-animal imaging. The proposed technique, Mueller-matrix optical coherence tomograph, (OCT), can image in real time the complete polarization properties of intact biological tissues for the first time at the microscopic scale (about 10 microns) in vivo. Optical polarization properties are sensitive indicators of physiological states such as the collagen content and abnormalities of biological tissues such as necrosis, and they can provide novel contrast mechanisms for imaging. Initially, this technology will likely have an impact on small-animal experimental studies because it can reduce the number of animals needed and the time required to conduct a study and can also improve the temporal correlation of a study. In addition to the immediate applications, this technology has the potential to detect various superficial human diseases--such as oral, skin, cervical, colon, and bladder cancers as well as skin burns--that can be accessed either directly or endoscopically as already demonstrated by conventional OCT. Mueller matrices can completely characterize the polarization properties of any material. The applicants' group pioneered Mueller-matrix OCT and demonstrated that this new imaging modality reveals tissue structures that are not observable with conventional OCT. Striking polarization contrast has already been shown in burns by Mueller-matrix OCT. The specific aims of the proposed research are as follows, in which the animal experiments will have dual foci: the imaging of skin cancers (animal model 1) and the imaging of burns (animal model 2). Aim 1. Develop a free-space Mueller-matrix OCT system to image Mueller matrices of biological tissues with both depth and lateral resolutions in real time. Aim 2. Characterize the capability of the proposed system and understand the origin of OCT polarization contrast by imaging tissue samples ex vivo. Compare the Mueller-matrix images with the corresponding histological results from both conventional and polarization light microscopes and identify the relationships between the Mueller-matrix images and the histological structures. Aim 3. Further develop the free-space Mueller-matrix OCT system using fiber optics and construct a hand-held probe for in vivo applications. Compare the experimental results from the fiber-optic system with those from the original free-space system. Aim 4. Characterize the capability of the proposed hand-held probe by imaging skin cancers in vivo in a mouse model (animal model 1). Detect the location, size, and Mueller-matrix contrast of skin cancers in comparison with the histological results from both conventional and polarization light microscopes. Analyze and characterize the temporal progression of skin cancer in the animal model. Aim 5. Characterize the capability of the proposed hand-held probe by imaging skin burns in vivo in a mini-pig model (animal model 2). Detect the lateral extent, depth, and Mueller-matrix contrast of skin burns in comparison with the histological results from both conventional and polarization light microscopes. Analyze and characterize the temporal healing process of burns in the animal model.